Respiration drives phase synchronization between blood pressure and RR interval following loss of cardiovagal baroreflex during vasovagal syncope

Loss of the cardiovagal baroreflex (CVB), thoracic hypovolemia, and hyperpnea contribute to the nonlinear time-dependent hemodynamic instability of vasovagal syncope. We used a nonlinear phase synchronization index (PhSI) to describe the extent of coupling between cardiorespiratory parameters, systolic blood pressure (SBP) or arterial pressure (AP), RR interval (RR), and ventilation, and a directional index (DI) measuring the direction of coupling. We also examined phase differences directly. We hypothesized that AP-RR interval PhSI would be normal during early upright tilt, indicating intact CVB, but would progressively decrease as faint approached and CVB failed. Continuous measurements of AP, RR interval, respiratory plethysomography, and end-tidal CO2 were recorded supine and during 70-degree head-up tilt in 15 control subjects and 15 fainters. Data were evaluated during five distinct times: baseline, early tilt, late tilt, faint, and recovery. During late tilt to faint, fainters exhibited a biphasic change in SBP-RR interval PhSI. Initially in fainters during late tilt, SBP-RR interval PhSI decreased (fainters, from 0.65 ± 0.04 to 0.24 ± 0.03 vs. control subjects, from 0.51 ± 0.03 to 0.48 ± 0.03; P < 0.01) but then increased at the time of faint (fainters = 0.80 ± 0.03 vs. control subjects = 0.42 ± 0.04; P < 0.001) coinciding with a change in phase difference from positive to negative. Starting in late tilt and continuing through faint, fainters exhibited increasing phase coupling between respiration and AP PhSI (fainters = 0.54 ± 0.06 vs. control subjects = 0.27 ± 0.03; P < 0.001) and between respiration and RR interval (fainters = 0.54 ± 0.05 vs. control subjects = 0.37 ± 0.04; P < 0.01). DI indicated respiratory driven AP (fainters = 0.84 ± 0.04 vs. control subjects = 0.39 ± 0.09; P < 0.01) and RR interval (fainters = 0.73 ± 0.10 vs. control subjects = 0.23 ± 0.11; P < 0.001) in fainters. The initial drop in the SBP-RR interval PhSI and directional change of phase difference at late tilt indicates loss of cardiovagal baroreflex. The subsequent increase in SBP-RR interval PhSI is due to a respiratory synchronization and drive on both AP and RR interval. Cardiovagal baroreflex is lost before syncope and supplanted by respiratory reflexes, producing hypotension and bradycardia